homa mohseni kouchesfahani

Small extracellular vesicles (sEVs) have been recognized as a promising therapeutic modality due to their low immunogenicity, and the ability to penetrate biological barriers. They contain significant amounts of lipids, proteins, and microRNAs, effectively participating in intra- and inter-cellular communications. sEVs derived from mesenchymal stem cells (MSCs) are being explored as a potential therapeutic option due to their immunomodulatory, anti-inflammatory, antioxidant, and regenerative properties, offering advantages over stem cell transplantationbased treatments. Chemotherapy induces side effects on various organs, particularly those with high proliferative capacity, such as testicular tissue. Exposure to some groups of chemotherapeutic agents, such as cyclophosphamide, cisplatin, and doxorubicin can cause DNA damage and induce apoptosis in spermatogonia and primary spermatocytes. Chemotherapy has been shown to induce cellular stress in testicles, leading to testicular dysfunction and the activation of apoptotic pathways in response to external and internal stress. The current research aims to review the potential therapeutic advantages of sEVs derived from MSCs in addressing sperm abnormalities and male infertility resulting from chemotherapy. Several lines of evidence indicate that treatment with sEVs can reduce testicular tissue damage caused by chemotherapy by decreasing oxidative stress and inflammatory responses. sEVs boost the growth and motility of spermatogenic cells and protect them from apoptosis by activating internal pathways. Therefore, as a non-invasive approach, they have shown promising results in regenerating damaged spermatozoa and restoring spermatogenesis.

To overcome cisplatin resistance, the cytotoxicity of a novel antitumor agent on two ovarian cancer cell lines sensitive and resistant to cisplatin was investigated.

MTT assay and flow cytometry were performed to assess the cytotoxicity of a novel water-soluble Pd (II) complex, [Pd(bpy)(pyr-dtc)]NO3 (PBPD), on cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Furthermore, variations in the expression of drug resistance gene cluster of differentiation 99 (CD99), signal transducer and activator of transcription 3 (STAT3), octamer-binding transcription factor 4 (OCT4), and multidrug resistance mutation 1 (MDR1) were evaluated using Real-Time PCR.

The IC50 values of PBPD in resistant cells were higher than those in sensitive cells. Furthermore, PBPD has a deadlier effect on sensitive cells compared to resistant cells, and the cell survival rate is reduced over time. Flow cytometry revealed that PBPD enhanced the population of living-resistant cells while driving them to apoptosis. PBPD, on the other hand, has a greater effect on the living cell population and has dramatically shifted the population toward apoptosis and necrosis in the sensitive cells. Furthermore, gene expression analysis showed that when sensitive and resistant cells were treated with cisplatin, all resistance genes increased significantly relative to the control. In contrast to OCT4, MDR1, STAT3, and CD99 resistance genes were not significantly elevated in sensitive cells treated with PBPD compared to the control. Thus, the expression of resistance genes in resistant cells treated with PBPD was lower than cisplatin.

As a result, PBPD is a promising anticancer agent for CDDP-resistant ovarian cancer.

Nowadays, the use of natural materials in regenerative medicine is very important, especially using substances with calcium carbonate structure due to their similarity to the bone structure. In this study, the effect of Cerastoderma lamarcki shell and rice bran extract on stem cell proliferation and differentiation has been investigated.

First, crastoderma shells were collected and cut into small pieces. Its compounds were analyzed by X-ray diffraction. Finally, the structural features of shells were investigated by SEM. Stem cells were extracted and cultured from the umbilical cord of Whartonchr('39')s jelly. After cells seeding on the scaffold, cell survival was studied by MTT. Adhesion, morphology, and diffusion of cells on the shells were also examined by SEM. Cells were stimulated by osteogenic medium and osteoblastic differentiation by alkaline phosphatase activity was studied. Rice bran ethanolic extract was used. Cell survival was studied by MTT technique and osteogenic differentiation was studied by Alizarin Red staining.

MTT studies showed appropriate adhesion of cells on the scaffold and SEM studies also showed successful binding and their appropriate morphology on the scaffold. Alkaline phosphatase studies showed that osteogenic differentiation of cells on shells is significant. In another part of this study, we studied the survival and osteogenic differentiation of these cells in treatment with ethanolic extract of rice bran. MTT studies showed a dose-dependent decrease in cell survival in the presence of the extract. Alizarin staining also showed the differentiation potential of this substance.

The results showed the appropriate potential of these two natural substances in bone differentiation. However, further studies are needed to prove their effects.

Polycystic ovary syndrome (PCOS) is an endocrine system disruption that affects 6-10% of women. Some studies have reported the effect of Vitex agnus-castus (Vitagnus) on the hypothalamic-pituitary-gonad axis (HPG). This study was conducted to investigate Vitagnus effect on the expression of kisspeptin gene in a rat model of PCOS.
Thirty-two female rats were distributed into: control, Vitagnus-treatment (365 mg/kg for 30 days), PCOS (Letrozole for 28 days) and PCOS animals treated with Vitagnus (30 days of Vitagnus after PCOS induction). At the end of the treatments, serum and ovaries were collected for analysis. Expression level of KISS-1 gene in the hypothalamus was investigated, using Real-Time-PCR.
In the PCOS group compared to control, FSH, progesterone and estradiol levels were decreased, whereas testosterone and LH levels were significantly increased. No significant changes were observed in the Vitagnus-treated animals in compare to control.  However, Vitagnus treatment in the PCOS group, resulted in a raise in progesterone, estrogen and FSH levels and a reduction in the levels of testosterone and LH. Quantitative gene expression analysis showed that PCOS induction resulted in over-expression of KISS-1 gene, however, Vitagnus treatment reduced this up-regulated expression to normal level.
In conclusion, our results indicated that Vitagnus extract inhibited downregulation of KISS-1 gene in the hypothalamus of PCOS rats. Because of the master role of kisspeptin in adjusting the HPG axis, Vitagnus is likely to show beneficial effects in the treatment of PCOS via regulation of kisspeptin expression. This finding indicates a new aspect of Vitagnus effect and may be considered in its clinical applications.

Sera are a multifaceted mixture of growth factors, proteins, and etc. which can influence oocyte maturation and fertilization. The aim of this survey is assessing the effect of different sera on in vitro maturation and fertilization in NMRI mice.

In this experimental study, maturation of oocytes was evaluated in α-MEM medium treated with 0 to 20 allogenic and autologous mice serums, Fetal Bovine Serum (FBS) and Bovine Serum Albumin (BSA) after 14-18h incubation period. Then MII oocytes were fertilized with capacitated sperms that percentages of 0 to 20 and investigated fertilization ratio.

In vitro maturation and in vitro fertilization level elevated significantly by adding serum to the culture medium (P<0.05). The most prominent maturation rate was observed in denuded oocytes (DOs) treated with FBS 10% (80%) and cumulus oocyte complex (COCs) treated with BSA 5% (98%) (P<0.001). In addition, the highest fertilization rate was observed in DOs treated with BSA 5% and COCs treated with allogenic serum 15% (77%, 75%), respectively (P<0.001).

The results of this study revealed that although BSA and FBS had better results than allogeneic and autologous sera, therefore, IVF findings in oocyte containing cumulus indicated high capacity of allogenic serum in this process. So, application of allogenic serum can be an appropriate replacement versus animal serum to reduce the challenges of infertility treatment modalities.

The aim of this blind randomised clinical trial study was to assess the clinical efficiency of combined density gradient centrifugation/Zeta (DGC/Zeta) sperm selection procedure compared to conventional DGC in infertile men candidates for intracytoplasmic sperm injection (ICSI). The literature shows that DGC/Zeta is more effective compared to DGC alone in selection of sperms with normal chromatin and improves the clinical outcome of the ICSI procedure. Therefore, this study re-evaluates the efficiency of DGC/Zeta in improving the clinical outcomes of ICSI in an independent clinical setting.

In this randomized, single-blind, clinical trial, a total of 240 couples with male factor infertility and at least one abnormal sperm parameter were informed regarding the study and 220 participated. Based on inclusion and exclusion criteria, 103 and 102 couples were randomly allocated into the DGC/Zeta and DGC groups, respectively. ICSI outcomes were followed and compared between the two groups.

Although there was no significant difference in fertilization rate (P=0.67) between the DGC/Zeta and DGC groups, mean percentage of good embryo quality (P=0.04), good blastocysts quality (P=0.049), expanded blastocysts (P=0.007), chemical pregnancies (P=0.005) and clinical pregnancies (P=0.007) were significantly higher in the DGC/ Zeta group compared to DGC. In addition, implantation rate was insignificantly higher in DGC/Zeta compared to DGC (P=0.17).

This is the second independent study showing combined DGC/Zeta procedure improves ICSI outcomes, especially the pregnancy rate, compared to the classical DGC procedure and this is likely related to the improved quality of sperm selected by the DGC/Zeta procedure (Registration number: IRCT20180628040270N1).

A recent innovative approach, based on induction of sublethal oxidative stress to enhance sperm cryosurvival, has been applied before sperm cryopreservation. The purpose of this study was to investigate the effects of different induction times of sublethal oxidative stress before cryopreservation on human post-thawed sperm quality.
In this experimental study, we selected semen samples (n=20) from normozoospermic men according to 2010 World Health Organization (WHO) guidelines. After processing the samples by the density gradient method, we divided each sample into 5 experimental groups: fresh, control freezing, and 3 groups exposed to 0.01 μM sodium nitroprusside (SNP) [nitric oxide (NO) donor] for 30 (T30), 60 (T60), or 90 minutes (T90) at 37˚C and 5% CO2 before cryopreservation. Motion characteristics [computer-assisted sperm analyser], viability, apoptosis [annexin V/propidium iodide (PI) assay], DNA fragmentation [sperm chromatin structure assay (SCSA)], and caspase 3 activity (FLICA Caspase Detection Kit) were assessed after thawing. The results were analysed by using one-way ANOVA and Tukey’s test. The means were significantly different at P Cryopreservation significantly decreased sperm viability and motility parameters, and increased the percentage of apoptosis, caspase 3 activity, and DNA fragmentation (P0.05).
Our results have demonstrated that the application of sublethal oxidative stress by using 0.01 μM NO for 60 minutes before the freezing process can be a beneficial approach to improve post-thawed human sperm quality.

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is the major cause of anovulation and consequent subfertility. In this study the effect of grape seed extract (GSE) on triglyceride (TG), total cholesterol (TC), highdensity lipoprotein-cholestrol (HDL-C), low-density lipoprotein-cholestrol (LDL-C) and interleukin-6 (IL-6) in PCOS Wistar rats were assessed.
In this experimental study, 84 adult female Wistar rats were divided into 7 groups (n=12) including control (intact), Sham (estradiol valerate solvent injection), control PCOS and 4 experimental PCOS groups. To induce the syndrome, a single subcutaneous injection of 2 mg estradiol valerate was applied. In experimental groups, PCOS rats were treated with different doses of 50, 75, 100 and 200 mg/kg body weight (BW) GSE by intraperitoneal injection for 10 consecutive days. After harvesting blood serum, TG was measured by Glycerol-3-phosphate Oxidase-Peoxidase (GPO- PAP), TC by Cholesterol Oxidase-Peroxidase (CHOD-PAP), and HDL-C by sedimentation method, LDL-C by Friedwald calculation and IL-6 by ELISA method. The serum values of each parameter were analyzed using one-way ANOVA at P≤0.05.
In all experimental groups significant decrease of visceral fat was obvious as compared with control PCOS group. LDL-C, TC and IL-6 levels in experimental groups, particularly at dose of 50 mg/kg of GSE, were significantly decreased as compared with PCOS group. However, HDL-C levels were not significantly changed.
According to the findings of this study, it can be concluded that GSE with its effects on serum TC, LDL-C and IL-6 could reduce the effects of dyslipidemia and inflammation in PCOS rats and improve systemic symptoms of PCOS.

Methotrexate (MTX) is an antimetabolite drug commonly prescribed for the various cancers and autoimmune diseases. Despite its considerable therapeutic effects, nephrotoxicity is the most important side-effect of treatment with MTX. Aquaporin1 (AQP1) is a water channel proteins which is present in mammalian kidney. Raspberry fruit with antioxidant properties is able to protect biological systems from the harmful effects of free radicals. The purpose of this study was to investigate the effect of raspberry extract on expression of AQP1 and the MTX-induced nephrotoxicity in rats.
In this experimental study, 60 adult male Wistar rats were divided into nine groups including control, sham, MTX treated group [single dose of 20 mg/kg of body weight (BW) MTX at the third day], raspberry treated groups [intraperitoneal (I.P) injection of 100, 200, 400 mg/kg of BW raspberry extract for ten consecutive days], MTX and raspberry treated groups. At day 11, rats were sacrificed via chloroform inhalation and kidney tissues were fixed in formalin solution for histological and immunohistochemistry analysis. The serological assays for urea, creatinine, uric acid and interleukin-6 (IL-6) levels were also performed.
MTX elevated serum level of the urea, creatinine, uric acid, IL-6, renal tissue damage and decreased the AQP1 expression level. Raspberry fruit extract improved the kidney function and reduced side effects of MTX in treated rats. Expression of AQP1, in a dose dependent manner was also ameliorated, as compared to control group.
According to the findings of this study, it can be concluded that biological activity of compounds presented in raspberry fruit extract especially anthocyanins may have chemo-protective effect on kidney function and AQP1 expression in rats treated by MTX.

Small molecule Purmorphamin (PMA) is the agonist of smoothened protein in Sonic hedgehog (Shh) signaling pathway. Effect of purmorphamin small molecule on differentiation of mesenchymal cells into bone tissue has been studied previously. Use of Shh causes progression of neural differentiation, and the differentiated cells express specific neural markers. Neurofilament (NF) and acetylcholine esterase (Chat) are specific markers of motor neurons and their expression in differentiated cells indicates their conversion into motor neurons. The aim of this study was to evaluate the ability of PMA to differentiate the human endometrial stem cells (hEnSCs) into motor neurons.
This analytical study was done in Tehran University of Medical Sciences laboratory on September of 2015. In this study hEnSCs were enzymatically extracted from endometrial tissue. After third passages, the flow cytometry was done for mesenchymal stem cells markers. The mesenchymal stem cells were divided into control and differentiated groups. FBS 10%ು೼嵶 was added to the culture medium of control group and the differentiating group was treated with differentiating medium containing N2, PMA, DMEM/F12, FBS, B27, IBMX, 2ME, FGF2, RA, BDNF. After 21 days immunocytochemistry (ICC) test was done for the expression of NF and Chat proteins and Real-time PCR analysis for expression of neural markers such as NF, Chat, Nestin and GFAP (as glial marker) at mRNA level.
The flow cytometry analysis showed that hEnSCs were positive for mesenchymal markers CD90, CD105 and CD146 and negative for endothelial marker CD31, and hematopoietic marker CD34. The immunocytochemistry and Real time-PCR results showed that the cells treated with PMA expressed motor neuron markers of NF and Chat.
According to the results of this study, it can be concluded that small molecule PMA has the potency to induce the differentiation of hEnSCs into neural cells, specifically motor neurons by activating Shh signaling pathway.

Paclitaxel is a chemotherapy drug inhibiting cell growth. In some studies, patients with normal liver function have experienced increase in bilirubin, ALT and AST by using paclitaxel. The aim of this study was to evaluate the ef-fect of intra-peritoneal injection of doses 5 and 10 mg/kg nZnO on the liver of rats treated with paclitaxel. 35 adult fe-male Wistar rats were divided into 7 groups including control, sham (saline injection), experimental groups1 and 2 (nZnO injection), experimental group 3 (paclitaxel injection), experimental groups 4 and 5 (nZnO and paclitaxel inje-ction). Liver function was examined 28 days after the end of injection. Experimental group3 had large and swollen liver morphology. Most hepatocytes had dense nuclei and changed cell shape indicating of cell death. Blood test showed si-gnificant increase in the levels of ALT, AST and bilirubin and decrease in the level of ALP in comparison with the co-ntrol group. In experimental groups 4 and 5, cell shape alterations, increase in cell death and increase in liver markers were remarkably reduced in comparison with the experimental group 3, in a way that there were no significant differ-ences with the control group. No significant differences were observed between the control group and experimental gr-oups 1 and 2. According to the findings, nZnO can reduce the side effects of paclitaxel on liver tissue.

Endometrial stem cells (EnSCs) were identified for the first time in 2004. These cells are capable of extensive self-renewal and have the potency to differentiate into chondrocyte, osteocyte, adipocyte, neuron and oligodendrocyte. PI3K/Akt signaling has been implicated in multiple cellular and organ functions, including differentiation, survival and cell death and its inhibition leads to cell differentiation. The purpose of this study was to investigate the differentiation of endometrial stem cells into neural cells by inhibition of PI3K/Akt pathway using small molecule Ly294002.
Endometrial tissues were treated enzymatically and segregated cells were cultured in DMEM/F12 with 10% FBS. The flow cytometry analysis was perfomed for CD105, CD90, CD146, CD31 and CD34 at the third passage. Then the neurogenic differentiation was evaluated at the third passage, 21 days after induction with differentiation media. Immunocytochemistry and Real-time PCR were performed to investigate the expression of specific neural stem cells markers.
The flow cytometry analysis showed that EnSCs were positive for CD90, CD105 and CD146 and negative for CD31 and CD34. Immunocytochemistry showed that the expression of nestin, NF and Chat neuronal markers in the cells treated with small molecule Ly294002. Real-time PCR also indicated expression of NF and Chat neuronal markers at the mRNA level.
According to the findings of this study it can be concluded that the EnSCs have neural differentiation potency in the suitable differentiation milieu. Ly294002 small molecules by inhibiting PI3K / Akt pathway possibly can prevent cell proliferation and induce cell differentiation

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory and cognitive dysfunction due to neuronal cell loss in higher brain centers. Senile plaques containing amyloid β (Aβ) are associated with this disease as well as a reduction in cholinergic neuron numbers. Tacrine is a reversible cholinesterase inhibitor in clinical use to treat moderate forms of AD. Chitosan nanoparticles represent an effective systemic delivery system for drugs. The application of tacrine-loaded chitosan nanoparticles has been shown to selectively increase tacrine concentrations in the brain tissue. In this study, we compared magnetic and non-magnetic tacrine-loaded chitosan nanoparticles for their bioactivity and neuroprotective potency in streptozotocin (stz)-induced neurodegeneration, an accepted animal model for AD. Male rats received a single injection of stz via an implanted cannula into the lateral brain ventricle. Tacrine (tac)-loaded chitosan nanoparticles were delivered into the tail vein. Spatial learning and memory were analyzed using the Morris water maze task. Amyloid precursor protein gene (APP) and seladin-1 gene expression were studied in the hippocampus by real time-PCR. Tac-loaded non-magnetic and tac-loaded magnetic chitosan nanoparticles improved spatial learning and memory after stz treatment with magnetic nanoparticles being most effective. Similarly, tac-loaded chitosan nanoparticles increased seladin-1 and reduced APP gene expression. Again, magnetic nanoparticles were more effective. These data reveal that tac-loaded non magnetic and tac-loaded magnetic chitosan nanoparticles to a higher extent improve brain deficits related to stz application. We conclude that the magnetic target drug delivery system is a promising therapeutic strategy to protect AD-related degenerating in the CNS.

Oximes are important materials in organic chemistry. Synparamethyl benzaldehyde oxime (toloaldoxime) is structurally similar to other oximes, hence we have studied its effects on the neonatal and adult female Balb/c mice reproductive systems in order to provide a platform for future studies on the production of female contraceptive drugs. In experimental study, we studied the effects of toloaldoxime on ovary growth and gonadal hormones of neonatal and adult Balb/c mice. A regression model for prediction was presented. The effects of toloaldoxime on neonatal mice were more than adult mice. The greatest effect was on the number of Graafian follicles (59.6% in adult mice and 31.83% in neonatal mice). The least effect was on ovary weight, and blood serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). According to the data obtained, toloaldoxime can be considered an antipregnancy substance.

In recent years the increasing use of nanoparticles has led researchers to study their effects on biological systems. The most important effects of nanoparticles on cells are their ability to induce or suppress production of reactive oxygen species (ROS). Changes in reactive oxygen species play an important role in various developmental processes, including proliferation and differentiation in several diseases such as Parkinson. The aim of this study was to investigate the effect of iron oxide nanoparticle with dimensions of less than 20 nanometers on the viability and neuronal differentiation of mouse embryonic stem cell (Royan B1). To assess the effects of Fe2O3 nanoparticles on neuronal differentiation of Royan B1 cells, embryoid bodies were divided into eight groups receiving different amounts of nanoparticle (10, 20, 30 μg/mL) for 12 hours, retinoic acid (1 μM), and both. Differentiation was examined under phase contrast microscope and using immunocytochemistry. Data analysis showed that cell death was increased by a time and concentration manner and there was a direct relevance between iron oxide amount and H2O2 level in cells. Statistical analysis of embryoid bodies showed that neural differentiation of mouse embryonic stem cells in groups that received nanoparticles were significantly lower than other groups and their viability were considerably reduced. According to the findings of this study it can be concluded that iron oxide nanoparticles reduce retinoic acid-neuronal differentiation in mouse embryonic stem cells and it seems that the main mechanism involved in the reduction of viability and neural differentiation was enhanced levels of ROS within the cells.

Wharton's Jelly Mesenchymal Stem Cells (WJMSc) are potential renewable source of cells in replacement therapies of many diseases. Different biomaterials have been used as a scaffold to mimic the stem cell niche, which is important for promoting cellular interactions, cell proliferation and differentiation. Encapsulation involves entrapment of living cells within the semi-permeable membrane for the exchange of nutrients, oxygen and stimuli, whereas antibodies and host immune cells are kept out. In this study, a new approach for culturing and differentiating Wharton's Jelly Mesenchymal Stem Cells to definitive endoderm in a three dimensional environment using alginate capsules is presented. In this experimental study, Wharton's Jelly Mesenchymal Stem Cells were capsulated and Trypan blue exclusion method was applied to determine cells viability. Then, encapsulated cells have been cultured in medium contain differentiating factors and to investigate the expression of definitive endoderm related genes, Real- time PCR was performed. The encapsulation procedure did not alter the morphology and viability of the encapsulated cells. Post-differentiation analysis confirmed the expression of FOXa2 and SOX17 as definitive endoderm specific markers. Alginate has potential to be used as a three dimensional scaffold for culturing and differentiation of WJMSCs to definitive endoderm.

Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with long wave ultraviolet A (UVA). In an experimental study, we aimed to demonstrate the effect of methoxsalen, UVA and their combination on oogenesis Balb/C mice. There were two experimental groups and a control group. The experimental groups were composed of i. a short term group with treatment duration of 15 days and ii. a long term group with treatment duration of 5 weeks. Both the long term and short term experimental groups were further subdivided into a UVA group, a methoxsalen group and a methoxsalen plus UVA group. After treatment, mature females in prosterus phase of ovarian cycle were scarified with ether, while their ovaries were removed and prepared for histological studies. Both macro and microscopic studies showed significant anomalies (p<0.05) among experimental group ovaries as compared to control group. The obtained results showed a significant decrease in the following factors: number and diameter of corpus lutei, Graafian follicles, diameter of granulosa cell layer and oocytes, number of primordial،and primary and growing follicles, while we observed an increase in number of atretic follicle. Furthermore, our findings confirmed an increase in theca diameter only through UVA treatment. Methoxsalen also reduced circulating estrogen levels in blood serum, significantly. Other cases of teratogenecity, such as follicles with three oocytes and disorganization in corpus luteum cells were observed. The result suggests that UVA, methoxsalen and their combination cause health problems and cell injuries.

Crown ethers are host molecules of metallic and nonmetallic ions. The capability of crown ether in the controling of cellular cycle and changing the activiti of some enzyme has been reported. In this study the effect of new crown ether (sulfoxo-bilactam-21-crown -7) on testis tissue and spermatogenesis has been investigated. In this experimental study, 24 mice were allocated to three groups. Control group did not receive anything, while Sham-operated group received Tween 80 and experimental group received new crown ether (sulfoxo-bilactam-21-crown-7). LD50 of drug was considered as 40 mg/kg. Then dose of 20 mg/kg crown ether was injected intraperitoneally once every day for one week. Two weeks after the last injection, animals were anesthetized and dissected. Blood was collected intracardically for hormonal assay. The testis were extruded and then fixed for histological studies. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey test. Intraperitoneal injection of sulfoxo-bilactam-21-crown-7 (20 mg/kg) did not show significant changes in the number of type A and B spermatogonia, primary spermatocytes and leydig cells in the experimental group compared to the control and Sham-operated groups. There was a significant increase in the level of testosterone (P<0.001) and a significant reduction was seen in the number of spermatids (P<0.05) and spermatozoa (P<0.001) in the experimental group compared to the control and Sham-operated groups. The results indicate that sulfoxo-bilactam-21-crown-7 diminishes the reproductive system activity and might be useful as a substance for birth control process

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. In this study, we examined all 10 exons to determine the most common mutations in MEFV gene as a single gene associated with FMF. In this basic study, 51 clinically diagnosed Iranian FMF patients referred to Taleghani hospital were studied. Peripheral blood was gained from them and genomic DNA was extracted according to phenol chloroform standard protocol. They were screened for the MEFV mutation using bidirectional sequencing and finally, the sequences were analyzed by related soft wares. Of 51 patients suspected to FMF, 24 (47.05%) were positive for mutation and 27 (52.95%) had no mutations. 14 patients had M694V mutation in exon10 including 4 homozygote mutation, 8 heterozygote and 4 compound heterozygote. Moreover, we could find 6 patients with M680I mutation and 2 individual (8.3%) with V721I mutation in exon 10. Only one person carried E148Q heterozygote mutation in exon 2. Our finding were compatible with others investigation that M694V mutation is the most common mutation in different populations.

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorders in women affecting 5-10% of women of reproductive age with abnormal cycles and hyperandrogenism. This syndrome represents an autoimmune disease that demonstrates high concentration of antiovarian antibodies. Bee venom with its immune reaction and its anti-inflammatory–like action works 100 times stronger than hydrocortisone. The aim of this study was to investigate the therapeutic effect of bee venom on the polycystic ovarian syndrome in rats.

The induction of PCOS was achieved by subcutaneous single injection of 2mg Estradiol valerate (EV) dissolved in sesame oil in estrous phase of ovarian cycle adult wistar rat. Sixty days after EV treatment 0.2mg/kg body weight of bee venom were injected intraperitoneally for 10 days. Rats were sacrificed and ovaries were removed to evaluate histopathological and histomorphometrical changes in EV- induced PCOS, bee venom treatment and normal intact animals. The tissues were processed routinely, paraffin blocks were made and 6-7 micron were prepared and stained with hematoxylin & eosin.

Thickness of granuloza layer, theca, number and diameter of cysts and number of atretic follicles were measured and showed a significant improvement (p<0.05) in indicated parameters in bee venom treated rats. Moreover, in more than 70% of cases, corpus luteum was observed in bee venom treated ovary, the condition that didnt observe in PCOS, indicating re- ovulation.

Bee venom is a new approach for induction of ovulation in patients with resistant polycystic ovarian disease. It is safe, easy to use, and lacks major side effects.

Hydrocephalus is a condition in which there is an abnormal build-up of cerebrospinal fluid within the ventricles and/or subarachnoid space, which leads to elevated intracranial pressure (ICP). VEGF is the prime hypoxia inducible angiogenic factor. We assumed that increased ICP leads to reduced oxygen tension in brain tissue, which triggers VEGF gene transcription so, in the current work we aimed to study VEGF alternation in hydrocephalus. Measurements were performed on CSF and serum aliquots obtained from control (n=20) and hydrocephalic patients (n=25), age- and sex-matched, were collected by lumbar puncture (LP) in the children hospital medical center of Tehran from 2006 to 2008. VEGF and total protein concentrations were determined by enzyme-linked immunosorbent assays (ELISA) and Bradford method, respectively. VEGF and total protein concentrations were significantly elevated in hydrocephalus CSF samples compared with those in controls (p<0.05, p<0.001, respectively). There was only a slight insignificant elevation in serum VEGF concentrations. Under normal conditions there is only diffuse expression of VEGF in the brain. In contrast, under local or systemic hypoxia, neurons, astrocytes, and microglial cells all show enhanced VEGF expression. The present study shows that VEGF concentrations are much higher in the CSF of children with hydrocephalus than in control samples and VEGF may be involved in hydrocephalus pathophysiology.

Stem cells (SCs) have great therapeutic indication due to their potency of self-renewal, multilineage differentiation, feasibility and safety for donors. In this study, adult mouse lung extracts containing hematopoietic growth factors were administered to umbilical cord, and evaluated the differentiation of umbilical cord stem cells into erythroid and myeloid lineages. In this basic and practical research, SCs were isolated from umbilical cord by enzyme digestion and cultured in appropriate culture medium. Subjects were divided into four groups: Experimental groups 1 and 2 (E1 and E2) which were exposed to 50% and 70% concentration of lung extract for 7 days, respectively, sham (Sh) group which did not exposed to lung extract and cultured for 7 days, and control group (C). E1, E2 and Sh groups were incubated for 7 days. All groups were evaluated by alkaline phosphatase detection kit for stem cells. Then, blood cells count and hematopoietic growth factors were assessed. ANOVA was used for data analysis. There were significant changes in E2 groups as compared with Sh and C groups, so that E2 group cells were differentiated into erythroid and myeloid lineages. Growth factors in lung extract could have stimulatory effects on umbilical cord stem cell differentiation into blood cells.

There are few studies on the heart development in vitro conditions. The aim of this study was to determine the maintenance time and development of heart in vitro conditions compared with in vivo, and evaluate the effects of electromagnetic field and L-Arginine on the heart development. In this experimental study, hearts of 11- day mice fetuses were excised and cultured in Medium 199, supplemented with 15% newborn calf serum in CO2 incubator in grid milipore membrane system. The culture period was 3 days at 370C in an incubator with 5% CO2 and 95% air. The isolated hearts were divided into sham group which received L-Arginine with no exposure to EMF, control group, and three experimental groups, including E1 which received EMF (50 HZ/7.83 mT for 30 minutes), E2 which received L-Arginine (350 mg/l) and E3 which received EMF and L-Arginine. Morphological and histological studies showed significant changes in experimental groups as compared with control groups. Length and diameter of heart, internal diameter of atrium and ventricle, length of interatrium septum and diameter of interventricular septum decreased significantly in experimental groups (p<0.001). Number of red blood cells and heart rate showed significant increase in experimental groups (p<0.001). Our findings suggest that electromagnetic field and L-Arginine have negative and disruptive effect on the mouse embryo heart development and have positive effect on the number of red blood cells and heart rate.

Retinoic acid (RA), one of the vitamin A derivatives, is used for the treatment of acne, psoriasis and some forms of cancer. It plays an important role in the growth and differentiation during development of vertebrates. In this research the effects of exogenous retinoic acid was investigated on forelimb and hind limb bud culture in vitro. In this experiment, female mice mated with males and observation of vaginal plug was considered as day 0 of gestation. The embryos were removed from uterus at day 12, their limb bud were excised and cultured in Eagle’s minimum essential media with 20% human embryo cord serum for two days. Experimental limb bud received RA in three concentrations of 10 -6,10 -5 and 10-4 M. Sham limb bud, received only alcohol (the solvent) and control did not receive anything. Samples were fixed in the Bouin’s solution and stained with Alcian blue for morphological features. Histological studies were morphologically examined. The toxic effects of RA exogenous on the development of limb buds were observed. This toxic effect was greater on fore limb bud. Our results showed that exogenous RA affects the growth and development of limb buds through reducing both the length of proximal–distal axis and the growth of digits in a dose-dependent manner. Microscopic studies revealed that RA hinders chondrogenesis in a dose-dependent manner with higher concentrations significantly reducing the number of limb bud chondrocytes

Acyclovir is a drug used to treat herpes virus infections including cold catch injuries, hot spots of genital organs, zona, AIDS, chicken pox and some other viral infections. The local cream of acyclovir is prepared in %5 packages, each gram containing 50mg of drug in a base of polyethylene glycol. Acyclovir cream (%5) in days 7, 8 and 9 of gestation was applied around their mouth (experimental group 1) and to the shared skin of other group (experimental group 2) twice a day in two hours intervals. Pregnant mice were sacrificed and dissected on day 15 of gestation and morphological and histological studies on the embryos and placenta were carried out. In the case of non-pregnant mice, the uteral born and ovaries were processed for histological investigations. Histological analyses showed significant decrease in embryogenesis and significant increase of abortion in experimental group 1 compared with control group. Significant increment was found in uterus diameter and thickness of endometrium when compared with control group. A pregnant woman should be very careful about applying acyclovir during the first trimester of pregnancy.